The contribution of edema toward brain swelling and intracranial pressure (ICP) rise particularly in cases of traumatic injury and tumor remains a critical problem. In head injured patients, raised ICP is the single most frequent cause of death. Brain edema, by definition is an increase in tissue water which for vasogenic, interstitial, and late ischemic brain edema results in an increase of extracellular fluid. The ultimate goal of this research is to understand the mechanisms by which edema is cleared from injured and diseased brain and the pathways by which this occurs. Knowledge of these mechanisms is fundamental to the development of new approaches to therapy. The complex inter-action of different mechanisms involved in resolution may be isolated by use of the experimental infusion model of brain edema where spatial distribution, total edema volume and chemical composition are precisely controlled. We plan to use this model in combination with gravimetric, chromatographic, electron microscopic, immunocytochemical and magnetic resonance imaging methods; to test hypotheses relating to elucidating mechanisms involved in early and late stages of clearance; to study the role that diffusion and colloid osmotic pressure play in the clearance process; to determine if injury is a necessary trigger for involvement of the astrocyte in clearance of water; and to assess if protein changes free and bound water fraction. This final objective will lead to the refinement of a non-invasive measure of brain edema in humans and will allow us for the first time to quantify edema in the injured brain.